Male pheromones ramp up aging in female worms

Male animals, through their invisible chemical “essence,” prime female animals for reproduction—but this also hastens the females’ aging process, according to a study with roundworms.

“The male signals trigger the female to ‘go for it’—to put more effort into reproduction—but then the body suffers,” says Ilya Ruvinsky, of the molecular biosciences department at Northwestern University. “There is a fine balance between reproduction and body maintenance, and this balance can be tipped by the male. We now are starting to tease apart this complexity.”

Using the tiny transparent roundworm C. elegans, a well-established model for biomedical research, researchers identified two distinct signals produced by males that affect female reproduction. The females sense the signals and respond by altering their physiology.

“We were investigating how animals reproduce under conditions that are closer to natural environments than the cushy life in the laboratory when we found this,” Ruvinsky says. “One signal causes an earlier onset of puberty in juvenile females. The other slows down aging of the reproductive system in mature females, keeping them fertile longer. However, it also speeds up aging of the body.”

A male animal doesn’t even have to be present to cause these changes in a female—a miniscule amount of two male pheromones is enough to affect aging. Pheromones are small molecules produced and released by animals into the environment to alter the physiology or behavior of other members of the species. Although the signals target reproduction, even sterile females—ones without eggs—experience these profound changes.

“Our results regarding puberty onset echo previous findings in mice,” Ruvinsky says. “In mammals, males also produce signals that manipulate the timing of sexual maturation of females. This raises an intriguing possibility that a basic mechanism controlling the rate of sexual development is similar in all animals. Because of this universality, our findings may have implications for humans.”

Fortunately, the research suggests that the effects on sexual maturation, the reproductive system, and overall body health can be separated, providing an area for future study. Understanding these basic mechanisms could lead to therapies that delay puberty and prolong fertility in humans as well as combat aging.

Published in the journal Current Biology, the study offers a simple explanation for a curious biological phenomenon: Male signals do not so much aim to harm females, but instead act to maximize females’ readiness for reproduction. “The harmful effects appear to be collateral damage, rather than the goal,” Ruvinsky says.

For the study, the researchers used genetics and imaging to characterize female responses to male signals, including prolonged fertility and decreased longevity. They also demonstrated that steroid hormones, which are involved in a wide variety of developmental and physiological processes in all animal species, play a key role in converting a male signal into faster sexual maturation in females.

The work was conducted using C. elegans because the simple organism of barely 1,000 cells is easy to manipulate, has a short lifespan, and offers a tremendous arsenal of experimental tools.

The Chicago Biomedical Consortium with support from the Searle Funds at The Chicago Community Trust funded the work that was conducted at the University of Chicago, where Ruvinsky and study coauthor Erin Z. Aprison were before moving to Northwestern.